Proprotein convertases (PCs) play critical roles in cleaving precursor
proteins (
growth factors,
hormones, receptors and adhesion molecules) for activation. PCs are implicated in a number of cellular functions, including
oncogenesis.
Endometrial cancer is the most common gynecological
cancer in the developed world, but the involvement of PCs is unclear. To characterize the role of PCs in
endometrial cancer, we assessed expression of seven PCs (PC1/3, PC2, PACE4, PC4,
furin,
PC5/6 and PC7) by RT-PCR in six well characterized
endometrial cancer cell lines. Expression was variable in all lines, with
furin being most consistently expressed in all cell lines tested. We next determined the cellular localization and expression levels of four ubiquitously expressed PCs (
furin, PACE4,
PC5/6 and PC7) in post-menopausal endometrial biopsies from control (n=7) and
endometrial cancer patients (
n=30) by immunohistochemistry.
Furin increased in
tumors, whereas
PC5/6, PACE4 and PC7 expression was reduced with increasing
cancer grades. Uterine lavage is a non-invasive source material for evaluating the endometrium. We thus assessed whether total PC activity was altered in uterine lavage of
endometrial cancer patients (n=36) compared to controls (n=10). PC activity was detected in all uterine lavage samples, and significantly elevated in all grades of
endometrial cancer. This study demonstrates a complex association between individual PCs and
endometrial cancer. Importantly, we show that monitoring the total PC activity in uterine lavage may provide a rapid and non-invasive method for the diagnosis of
endometrial cancer in postmenopausal women.